Mucosal immunity Flashcards
Barrier immunity
refers generally to immune systems associated with the skin and mucosal tissues
The tissues of the mucosal immune system are
the lymphoid organs and cells associated with the gastrointestinal, respiratory, and urogenital tracts, as well as the oral cavity, pharynx, middle ear, and the glands associated with these tissues, such as the salivary glands and lacrimal glands. The lactating breast is also considered part of the mucosal immune system.
Barrier organs are populated by
by innate and adaptive immune cells that interact with epithelium and secondary lymphoid tissue
Microbiome
the collection of all microbes, such as bacteria, fungi, viruses, and their genes, that naturally live on our bodies and inside us.
Adjacent IECs
form tight junctions that are essential to the function of the intestinal barrier and the regulation of movement of ions, solutes, and water across the intestinal epithelium
Tight junctions
are primarily composed of claudins and occludins, transmembrane proteins that undergo homotypic adhesions between adjacent IECs near their apical surfaces to form a continuous ‘ribbon’ that seals the intercellular junction (middle panel).
Epithelial cell types
Enterocytes
M cells
Goblet cells
Paneth cells
Enteroendocrine cells
Tuft cells
Transient amplifying cells
Stem cells
Paneth cells
Only present in the SI. Antimicrobial peptides and SC niche. Highly specialized secretory epithelial cells located in the small intestinal crypts of Lieberkühn
Tuft cells:
Specialized in response to Helminths. chemosensory cells in the epithelial lining of the intestines.
Enteroendocrine cells:
Sense nutrients and release hormones and neurotransmitters to regulate nutrients absorption and satiety. Hormone-producing cells that are sprinkled throughout the gut epithelium.
Mucus production roles
Produced by Goblet cells
Reduces mechanical stress
Trap microbes
Retain SIgA and AMPs
Colonization of commensals
ILCs
Innate Lymphoid Cells
Three types: ILC1, ILC2 and ILC3
ILC1
produce IFN-gamma – intracellular (virus and bacteria)
ILC2
produce IL-13 – Helminth
ILC3
produce IL-22 / IL-17A – Bacteria/fungi
ILCs are
a family of lymphocytes comprising the innate counterparts of T cells. They are poised to secrete cytokines that respond swiftly to pathogenic tissue damage and shape subsequent adaptive immunity.While lacking antigen-specific receptors, ILCs detect changes in the microenvironment through receptors for cytokines that are released upon tissue damage, as well as a broad range of receptors for nutrient components, microbial products, lipid mediators, and neuronal transmitters
ILCs are found
both lymphoid and non-lymphoid tissues
Regulatory T cells
TREG
Defined by expression of Foxp3 (transcription factor)
Helps with tolerance and suppresses response by communicating to other immune cells
TREG are made
Thymus during development (circulating)
in mesentyric Lymph Node through instruction by migrating dendritic cell
Immune tolerance
Absence of inflammatory response to commensal microbiota and food components
Lamina propria constituents send transepithelial dendrites to sample the lumen
Environment enriched in IL10 and TGFB
Production of secretory IgA (SIgA)
Type I (IFN-gamma, IL1b and IL18)immunity
Virus / intracellular bacteria
Type II (Il-4, 5, and 13) immunity
Helminth/Allergens/Venoms
Type III (IL-22, IL-17) immunity
Extracellular bacteria / fungi
Type I immunity is activated
Activation of PRRs triggers
TLR activation induces IL23 production that induces IL17 and IL22 production by Th17 and ILCs. IL22 induces anitimicrobials expression by IECs and IL17 attract neutrophiles
NOD activation leads to inflammasome and IL1b and IL18 expression. That induces IFNg by ILCs.
DCs migrate mesenteric Lymph Nodes (mLN) for Th1 expansion
B cells IgG class switching